OBJECTIVE: To determine the oncolytic efficacy of an attenuated form of myxoma virus lacking the serp2 gene in canine tumor cells. SAMPLE: Primary cells were isolated from tumors that were surgically removed from dogs and from connective tissue obtained from the cadaver of a dog. Cells of various established cell lines from tumors and nontumorous tissues were obtained. PROCEDURES: Experiments were performed with cells in monolayer culture. Cell cultures were inoculated with wild-type myxoma viruses or myxoma viruses lacking the serp2 gene, and measures of cytopathic effects, viral growth kinetics, and cell death and apoptosis were determined. RESULTS: Myxoma viruses replicated in cells of many of the primary and established canine tumor cell lines. Canine tumor cells in which expression of activated protein kinase B was upregulated were more permissive to myxoma virus infection than were cells in which expression of activated protein kinase B was not upregulated. Myxoma viruses lacking the serp2 gene caused more cytopathic effects in canine tumor cells because of apoptosis than did wild-type myxoma viruses. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study indicated myxoma viruses lacking the serp2 gene may be useful for treatment of cancer in dogs. Impact for Human Medicine-Results of the present study may be useful for development of novel oncolytic treatments for tumors in humans.
OBJECTIVE: To determine the oncolytic efficacy of an attenuated form of myxoma virus lacking the serp2 gene in caninetumor cells. SAMPLE: Primary cells were isolated from tumors that were surgically removed from dogs and from connective tissue obtained from the cadaver of a dog. Cells of various established cell lines from tumors and nontumorous tissues were obtained. PROCEDURES: Experiments were performed with cells in monolayer culture. Cell cultures were inoculated with wild-type myxoma viruses or myxoma viruses lacking the serp2 gene, and measures of cytopathic effects, viral growth kinetics, and cell death and apoptosis were determined. RESULTS:Myxoma viruses replicated in cells of many of the primary and established caninetumor cell lines. Caninetumor cells in which expression of activated protein kinase B was upregulated were more permissive to myxoma virus infection than were cells in which expression of activated protein kinase B was not upregulated. Myxoma viruses lacking the serp2 gene caused more cytopathic effects in caninetumor cells because of apoptosis than did wild-type myxoma viruses. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study indicated myxoma viruses lacking the serp2 gene may be useful for treatment of cancer in dogs. Impact for Human Medicine-Results of the present study may be useful for development of novel oncolytic treatments for tumors in humans.
Authors: Ivaylo Gentschev; Sandeep S Patil; Ivan Petrov; Joseph Cappello; Marion Adelfinger; Aladar A Szalay Journal: Viruses Date: 2014-05-16 Impact factor: 5.048